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Novel oxygen sensing mechanism in the spinal cord involved in cardiorespiratory responses to hypoxia.

ABSTRACT: As blood oxygenation decreases (hypoxemia), mammals mount cardiorespiratory responses, increasing oxygen to vital organs. The carotid bodies are the primary oxygen chemoreceptors for breathing, but sympathetic-mediated cardiovascular responses to hypoxia persist in their absence, suggesting additional high-fidelity oxygen sensors. We show that spinal thoracic sympathetic preganglionic neurons are excited by hypoxia and silenced by hyperoxia, independent of surrounding astrocytes. These spinal oxygen sensors (SOS) enhance sympatho-respiratory activity induced by CNS asphyxia-like stimuli, suggesting they bestow a life-or-death advantage. Our data suggest the SOS use a mechanism involving neuronal nitric oxide synthase 1 (NOS1) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX). We propose NOS1 serves as an oxygen-dependent sink for NADPH in hyperoxia. In hypoxia, NADPH catabolism by NOS1 decreases, increasing availability of NADPH to NOX and launching reactive oxygen species-dependent processes, including transient receptor potential channel activation. Equipped with this mechanism, SOS are likely broadly important for physiological regulation in chronic disease, spinal cord injury, and cardiorespiratory crisis.

SUBMITTER: Barioni NO

PROVIDER: S-EPMC8956269 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Novel oxygen sensing mechanism in the spinal cord involved in cardiorespiratory responses to hypoxia.

Barioni Nicole O NO Derakhshan Fatemeh F Tenorio Lopes Luana L Onimaru Hiroshi H Roy Arijit A McDonald Fiona F Scheibli Erika E Baghdadwala Mufaddal I MI Heidari Negar N Bharadia Manisha M Ikeda Keiko K Yazawa Itaru I Okada Yasumasa Y Harris Michael B MB Dutschmann Mathias M Wilson Richard J A RJA

Science advances 20220325 12

As blood oxygenation decreases (hypoxemia), mammals mount cardiorespiratory responses, increasing oxygen to vital organs. The carotid bodies are the primary oxygen chemoreceptors for breathing, but sympathetic-mediated cardiovascular responses to hypoxia persist in their absence, suggesting additional high-fidelity oxygen sensors. We show that spinal thoracic sympathetic preganglionic neurons are excited by hypoxia and silenced by hyperoxia, independent of surrounding astrocytes. These spinal ox ...[more]

PMID: 35333571

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Project description:BackgroundTranscutaneous spinal cord stimulation (tSCS) is a non-invasive modality in which electrodes can stimulate spinal circuitries and facilitate a motor response. This review aimed to evaluate the methodology of studies using tSCS to generate motor activity in persons with spinal cord injury (SCI) and to appraise the quality of included trials.MethodsA systematic search for studies published until May 2021 was made of the following databases: EMBASE, Medline (Ovid) and Web of Science. Two reviewers independently screened the studies, extracted the data, and evaluated the quality of included trials. The electrical characteristics of stimulation were summarised to allow for comparison across studies. In addition, the surface electromyography (EMG) recording methods were evaluated.ResultsA total of 3753 articles were initially screened, of which 25 met the criteria for inclusion. Studies were divided into those using tSCS for neurophysiological investigations of reflex responses (n = 9) and therapeutic investigations of motor recovery (n = 16). The overall quality of evidence was deemed to be poor-to-fair (10.5 ± 4.9) based on the Downs and Black Quality Checklist criteria. The electrical characteristics were collated to establish the dosage range across stimulation trials. The methods employed by included studies relating to stimulation parameters and outcome measurement varied extensively, although some trends are beginning to appear in relation to electrode configuration and EMG outcomes.ConclusionThis review outlines the parameters currently employed for tSCS of the cervicothoracic and thoracolumbar regions to produce motor responses. However, to establish standardised procedures for neurophysiological assessments and therapeutic investigations of tSCS, further high-quality investigations are required, ideally utilizing consistent electrophysiological recording methods, and reporting common characteristics of the electrical stimulation administered.

Project description:IntroductionMales and females differ anatomically and functionally in cardiorespiratory regulation, with males tending to experience greater oxygen desaturation under hypoxia. Therefore, sex might moderate cardiorespiratory responses to acute hypoxia exposure. Accordingly, we hypothesized that sex differences in cardiovascular and ventilatory responses would be more pronounced with equal hypoxia duration (iso-time) but less pronounced at similar oxygen desaturation levels (iso-saturation).MethodsTwenty-two (12 females) healthy individuals were exposed to normoxia (10 min at FiO2 = 0.21) and hypoxia (10 min at FiO2 = 0.115), respectively. Pulse oxygen saturation (SpO2), R-R intervals, cardiac output, blood pressure (BP), and ventilatory data were continuously recorded during spontaneous breathing. Spectral analysis of R-R intervals and systolic BP revealed cardiovascular autonomic modulation in the low- (LF; 0.04-0.15 Hz) and high-frequency (HF; 0.15-0.40 Hz) bands and alpha-index (α-LF) assessed spontaneous baroreflex sensitivity (BRS). Sex differences were compared in iso-saturation and iso-time analyses.ResultsAt 10 min of hypoxia (iso-time), males desaturated more than females (interaction: p = 0.004), and hypoxia-induced tachycardia in both groups (p < 0.001), but no "sex-time" interaction was found for cardiovascular data. In contrast, only males responded with ventilatory responses during iso-time hypoxia, decreasing breathing frequency (interaction: p = 0.022) and increasing tidal volume (Vt) (interaction: p = 0.036). Otherwise, during iso-saturation (SpO2-matched ∼91%), heart rate and LF of R-R intervals increased more in females than in males (interaction: p = 0.049). However, only males increased Vt (interaction; p = 0.037).ConclusionOur data indicate that females counterbalance hypoxia mainly by systemic circulatory adjustments, while males use both, circulatory and ventilatory adjustments.

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Novel oxygen sensing mechanism in the spinal cord involved in cardiorespiratory responses to hypoxia.

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Novel oxygen sensing mechanism in the spinal cord involved in cardiorespiratory responses to hypoxia.

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